Estriol has different effects from 17β-estradiol in modulating mouse splenocyte function under inflammatory conditions

Abstract

Estriol (E₃), an endogenous estrogen predominantly produced during human pregnancy, has been suggested to play an important role in modulating the immune system function during pregnancy. The present study sought to investigate the ability of E₃ to alter splenocyte functions in non-immunized naïve BALB/c female mice and also in mice injected with complete Freund’s adjuvant (CFA), and the effect of E₃ was compared with that of 17β-estradiol (E₂). When mice were injected with CFA, their spleen weight index (i.e., wet organ wet/whole body weight) was increased by ~ 300%, but co-administration of E₃ almost completely suppressed splenomegaly. E₃ also reduced cytokine production and reduced ERK and p38 activation in both splenocytes and peritoneal exudate cells from CFA-treated animals. In comparison, while E₂ had a similar but slightly weaker effect than E₃ in reducing splenomegaly, it had a rather different effect from E₃ on cytokine production and ERK activation in splenocytes and peritoneal exudate cells from CFA-treated mice. Under naïve immunological conditions, E₃ and E₂ had very similar effects on splenocyte functions. Both of them transiently increased the percentages of splenic CD4⁺ and CD8⁺ cells. They also increased the proliferation of splenocytes ex vivo, and stimulated production of interferon-γ and interleukin-2. Altogether, these data show that E₃ and E₂ have different effects on splenocyte functions when the animals are under experimentally induced inflammatory conditions.

Keywords::

• 17β-Estradiol
• estriol
• immune modulation
• splenocytes
• immunological conditions

Acknowledgments

We thank Dr Xiao-Kang Li at the National Research Institute for Child Health and Development (Tokyo, Japan) for helpful discussion and suggestions regarding some of the experimental methods and assays. This study was supported, in part, by a grant from the National Institutes of Heath (ES015242). Some of the instruments employed in this study are part of the COBRE core facility that is supported by the NIH Grant P20RR021940 from the National Center for Research Resources.

Declaration of interest

The authors declare that there exists no conflict of interest that could be perceived as prejudicing the impartiality of the research reported here. The authors alone are responsible for the content and writing of the paper.